Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Is Associated with Indigenous American Ancestry in Latin American Women

• Published in: Cancer research (Chicago, Ill.) Vol. 80; no. 9; pp. 1893 - 1901
• Main Authors: Marker, Katie M, Zavala, Valentina A, Vidaurre, Tatiana, Lott, Paul C, Vásquez, Jeannie Navarro, Casavilca-Zambrano, Sandro, Calderón, Mónica, Abugattas, Julio E, Gómez, Henry L, Fuentes, Hugo A, Picoaga, Ruddy Liendo, Cotrina, Jose M, Neciosup, Silvia P, Castañeda, Carlos A, Morante, Zaida, Valencia, Fernando, Torres, Javier, Echeverry, Magdalena, Bohórquez, Mabel E, Polanco-Echeverry, Guadalupe, Estrada-Florez, Ana P, Serrano-Gómez, Silvia J, Carmona-Valencia, Jenny A, Alvarado-Cabrero, Isabel, Sanabria-Salas, María Carolina, Velez, Alejandro, Donado, Jorge, Song, Sikai, Cherry, Daniel, Tamayo, Lizeth I, Huntsman, Scott, Hu, Donglei, Ruiz-Cordero, Roberto, Balassanian, Ronald, Ziv, Elad, Zabaleta, Jovanny, Carvajal-Carmona, Luis, Fejerman, Laura
• Format: Journal Article
• Language: English
• Published: United States 01.05.2020
• Subjects: Adult; Aged; Asian People - ethnology; Asian People - statistics & numerical data; Black or African American; Black People - ethnology; Black People - statistics & numerical data; Breast Neoplasms - chemistry; Breast Neoplasms - ethnology; Breast Neoplasms - genetics; Colombia - ethnology; Female; Hispanic or Latino - genetics; Humans; Indians, North American; Indians, South American; Latin America - ethnology; Linear Models; Logistic Models; Mexico - ethnology; Middle Aged; Peru - ethnology; Receptor, ErbB-2 - analysis; Receptor, ErbB-2 - genetics; Receptors, Estrogen - blood; Receptors, Progesterone - blood; United States; White People - ethnology; White People - statistics & numerical data; Young Adult; Colombia; Mexico; United States; Peru; Latin America
• ISSN: 0008-5472; 1538-7445; 1538-7445
• DOI: 10.1158/0008-5472.CAN-19-3659

Women of Latin American origin in the United States are more likely to be diagnosed with advanced breast cancer and have a higher risk of mortality than non-Hispanic White women. Studies in U.S. Latinas and Latin American women have reported a high incidence of HER2 positive (+) tumors; however, the factors contributing to this observation are unknown. Genome-wide genotype data for 1,312 patients from the Peruvian Genetics and Genomics of Breast Cancer Study (PEGEN-BC) were used to estimate genetic ancestry. We tested the association between HER2 status and genetic ancestry using logistic and multinomial logistic regression models. Findings were replicated in 616 samples from Mexico and Colombia. Average Indigenous American (IA) ancestry differed by subtype. In multivariate models, the odds of having an HER2 tumor increased by a factor of 1.20 with every 10% increase in IA ancestry proportion (95% CI, 1.07-1.35; = 0.001). The association between HER2 status and IA ancestry was independently replicated in samples from Mexico and Colombia. Results suggest that the high prevalence of HER2 tumors in Latinas could be due in part to the presence of population-specific genetic variant(s) affecting HER2 expression in breast cancer. SIGNIFICANCE: The positive association between Indigenous American genetic ancestry and HER2 breast cancer suggests that the high incidence of HER2 subtypes in Latinas might be due to population and subtype-specific genetic risk variants.